title: Both miR-17-5p and miR-20a alleviate suppressive potential of myeloid-derived suppressor cells by modulating STAT3 expression.
abstract: Myeloid-derived suppressor cells (MDSCs) were one of the major components of the immune suppressive network. STAT3 has an important role in regulating the suppressive potential of MDSCs. In this study, we found that the expression of STAT3 could be modulated by both miR-17-5p and miR-20a. The transfection of miR-17-5p or miR-20a remarkably reduces the expression of reactive oxygen species and the production of H(2)O(2), which are regulated by STAT3. MDSCs transfected with miR-17-5p or miR-20a are less able to suppress Ag-specific CD4 and CD8 T cells. Importantly, both miR-17-5p and miR-20a alleviate the suppressive function of MDSCs in vivo. The expression of miR-17-5p and miR-20a in tumor-associated MDSCs was found to be lower than in Gr1(+)CD11b(+) cells isolated from the spleens of disease-free mice. Tumor-associated factor downregulates the expression of both miR-17-5p and miR-20a. The modulation of miR-17-5p and miR-20a expression may be important for the process by which patients with a tumor can overcome the immune tolerance mediated by MDSCs. Our results suggest that miR-17-5p and miR-20a could potentially be used for immunotherapy against diseases, especially cancer, by blocking STAT3 expression.
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
authors.forename: Qiaofei
authors.initials: Q
authors.lastname: Liu
authors.forename: Siping
authors.initials: S
authors.lastname: Mi
authors.forename: Xue
authors.initials: X
authors.lastname: Liang
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Su
authors.forename: Jinyi
authors.initials: J
authors.lastname: Liu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fenghua
authors.initials: F
authors.lastname: Guo
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rongcun
authors.initials: R
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C532375:Mirn20 microRNA, mouse; D050796:STAT3 Transcription Factor